Treatment burden and regimen fatigue among patients with HIV and diabetes attending clinics of Tikur Anbessa specialized hospital

Nascent studies showed that patients with chronic medical illnesses such as diabetes mellitus (DM) and HIV/AIDS are highly vulnerable to face both treatment burden and regimen fatigue. However, an attempt made so far in this sphere in sub-Saharan African health care context is dearth. Thus, this study aimed to determine the level of treatment burden and regimen fatigue of diabetic and HIV patients attending adult diabetic and ART clinics of TASH and explore patients’ and health care workers’ propositions to reduce treatment burden and regimen fatigue. An explanatory sequential mixed methods study was conducted at the adult HIV and DM clinics of TASH, Addis Ababa, Ethiopia from February 01-March 30, 2022. Simple random and purposive sampling techniques were employed to select participants for quantitative and qualitative studies, respectively. Descriptive analysis was done to summarize the quantitative data. Logistic and linear regression analyses were performed to identify predictors of treatment burden and regimen fatigue, respectively. P value < 0.05 was considered statistically significant. Qualitative data was analyzed by using a thematic analysis. A total of 300 patients (200 diabetes and 100 HIV) were included in the quantitative study. For the qualitative study, 14 patients and 10 health care workers (six nurses and four medical doctors) were included. Participants' mean global Treatment Burden Questionnaire (TBQ) and Treatment Regimen Fatigue Scale (TRFS) score were 28.86 ± 22.13 and − 42.82 ± 17.45, respectively. Roughly, 12% of patients experienced a high treatment burden. The presence of two or more comorbidities (adjusted odds ratio [AOR] = 7.95, 95% confidence interval [CI] 1.59–39.08), daily ingestion of more than five types of prescribed medications (AOR = 6.81, 95%CI 1.59–29.14), and good knowledge about DM and/or HIV (AOR = 0.33, 95%CI 0.12–0.92) were predictors of treatment burden. Poor availability of medications (β = 0.951, p < 0.001) was the only predictor of regimen fatigue. Patients and health care workers primarily proposed to foster self-care efficacy, advance administrative services of the clinic and hospital, and improve healthcare system provision. The findings of this study unveiled that a considerable proportion of patients experienced low levels of treatment burden and regimen fatigue. This study showed that boosting the patients’ self-care efficacy, upgrading administrative services of the clinic and hospital, and promoting the healthcare system provision had enormous significance in reducing treatment burden and regimen fatigue. Therefore, when designing patient-specific healthcare interventions for both HIV and diabetic patients’ various factors affecting both treatment burden and regimen fatigue should be considered to achieve the desired goals of therapy.


Study setting, study design and study period
This study used an explanatory sequential mixed methods design.Consequently, a quantitative (cross-sectional) investigation was followed by a qualitative study.From February 1 to March 30, 2022, the study was conducted at TASH's ambulatory ART and diabetes clinics in Addis Ababa, Ethiopia.TASH is Ethiopia's largest governmentowned tertiary care, specialized, referral, and teaching hospital.It has 51 specialty and sub-specialty out-patient clinics that serve around 500,000 patients per year 17 .The ART and DM clinics are part of a larger network of specialized clinics that offer full care, including treatment and follow-up.The DM clinic is open three days a week (Monday, Wednesday, and Friday), but the ART clinic is open five days a week (excluding weekends).Every day, on average, 70 diabetics and 50 HIV patients come for follow-up.

Study participants
All adult HIV and diabetes patients who visited TASH's respective ambulatory clinics on a regular basis and met the inclusion criteria during the study period were included.Patients were eligible for enrollment in this study if they were at least 18 years old, had been diagnosed with HIV or/and diabetes for at least 6 months prior to the study, had regular follow-up at TASH's ART and DM clinics, had been on treatment for at least 6 months, and could complete a written consent form.Patients with cognitive disabilities who may have difficulty understanding questions and critically sick patients who cannot tolerate interviews were excluded.

Sample size calculation and sample size determination
The sample size was estimated using a single population proportion calculation with a 95% confidence level, 5% margin of error, 50% proportion of TB and TRF, expected number of source population (N = 4240), and 5% non-response rate.As a result, a total sample size of 370 patients was determined.70 patients (30 from the diabetic clinic and 40 from the ART clinic) were excluded, leaving 300 patients (200 from the diabetes clinic and 100 from the HIV clinic) in the final analysis.The main reasons for exclusion were unwillingness to participate in the study and intolerance to complete in-depth interview.
To identify study participants who met the stated inclusion criteria for the quantitative investigation, a simple random selection procedure was used.As a sampling framework, the nurse appointment logbook was used.Patients were included in the research at random during their drug refill appointment.Purposive sampling was used to collect detailed information from patients and health care staff for the qualitative investigation.As a result, from each clinic, 7 patients and 5 health care staff were chosen.The qualitative study included 14 patients (7 females) and 10 health care providers (6 females and 4 males).
Six experienced nurses and four medical doctors (1 senior endocrine specialist, 1 senior infectious disease specialist, 2 fellowship residents, and 1 chief R3 resident) made up the health care team.Patients were chosen for in-depth interviews based on their TBQ and TRFS global scores, whereas health care personnel were chosen for key informant interviews based on their experience and knowledge with diabetes and HIV/AIDS management.After a brief explanation of the study by the matrons of the two clinics, eligible patients and health care personnel were reached through oral invitation and invitation letter, respectively.The participants who had only accepted the invitation offer were then contacted by phone to set up a convenient date and time for the interviews.

Study variables
Dependent variables: (1) treatment burden, (2) treatment regimen fatigue.Independent variables: (1) sociodemographic characteristics include age, sex, place of residence, occupation status, monthly income level, marital status, education level, smoking habit, and living conditions.(2) Clinical characteristics include duration of DM/HIV/AIDS, duration of treatment, severity of DM/HIV, presence and number of comorbidities, travel time, number of appointments, number of hospitalizations during the past 12 month, knowledge about DM/HIV/ AIDS, and health literacy.(3) Treatment-related characteristics include total number of prescribed medications/ pills, medications source, medication type, costs of medications, availability of medications, and ADR.

Data collection instruments and procedure
The current investigation was divided into two basic parts.In phase I, standardized questionnaires were used to collect quantitative data on the patients' sociodemographic, clinical, and therapeutic features, as well as their level of TB and TRF.Patients' medical records were also checked to augment additional clinical data if needed.The Treatment Burden Questionnaire (TBQ-15) and Treatment Regimen Fatigue Scale (TRFS) were used to assess diabetic and HIV patients' treatment burden and regimen tiredness, respectively.The TBQ and TRFS were administered by two nurses having MSc degrees.On average, quantitative data gathering took 30 min.
The TBQ-15 is a well-validated universal psychometric instrument consisting of 15 items with scores ranging from 0 (no burden) to 10 (extremely high burden) that assesses the burden associated with medication management, self-monitoring, laboratory tests, doctor visits, the need for organization, administrative tasks, diet, physical activity, social impact, and financial burden of patients.It has five dimensions: medication-related hardship, administrative burden, financial burden, lifestyle modification burden, and social life-related burden 18 .The TRFS is a simple and reliable self-report psychometric instrument used to assess the amount of TRF in patients with chronic conditions who are on long-term treatment regimens.It consists of 22 items that examine three dimensions: treatment motivation, cynicism, and self-efficacy 19 .
Permission to utilize the TBQ and TRFS, as well as authorization to translate them, were secured from the original developers via Mapi Research Trust (MRT) and the corresponding author, who conducted the initial validation research, respectively.As previously described in our pioneering published work, a strict translation approach was employed 20 .In the current study, the Cronbach alpha values for the Amharic for Ethiopia versions of TBQ-15 and TRFS were 0.76 and 0.81, respectively.However, other than internal consistency, no additional psychometric testing was performed.
In phase II, semi-structured interviews were used to collect qualitative data on patients' and health care staff ' suggestions for reducing TB and TRF.In-depth and key informant interviews lasting around 30 min were conducted utilizing an interview guide adapted from diverse literatures.Face-to-face cognitive interviews with 10 patients and 5 health care personnel were used to ensure the comprehensibility of the opening question and the usability of potential reformulations and explanations.Furthermore, the face and content validity of the data collection devices were investigated by four highly qualified professionals in clinical research and diabetes/ HIV/AIDS management.Two clinical pharmacists with master's degrees and extensive prior experience in qualitative-based health research conducted the interviews face-to-face in a separate quiet room adjacent to the DM clinic's matron's head station.
Principal investigators adequately trained data collectors for two consecutive days on the strict application of study criteria, explanation of study objectives, obtaining written consents, implementation of sampling techniques, uniform interpretation of questions, and the confidentiality of collected data.To record information from the interviews, voice recorders and notebooks were employed.Interviews were performed until the information was exhausted.Finally, the results of both phases I and II were evaluated to provide a thorough understanding of TB and TRF.

Data analysis
The quantitative data was input and cleaned in Epi Info version 4.6.0.2 before being exported and analyzed in the Statistical Package for the Social Sciences (SPSS) version 26.To summarize the categorical variables, frequencies and proportions were used.The mean, standard deviation, and/or median (IQR) of continuous variables were provided.Initially, normality tests utilizing plots and the Shapiro-Wilk test were used to choose relevant and robust statistical tests for continuous data.In addition, the variance inflation factor (VIF) was used to examine correlation among predictor variables.For excluding collinearity, a VIF of 10 was chosen as a cut point.
To analyze the relationship between treatment load and all independent variables and to identify candidates for multivariable analysis, binary logistic regression analysis was used.To find predictors of treatment burden, independent variables having p values less than 0.25 in univariable binary logistic regression analysis were reentered into a multivariable binary logistic regression model.Statistical significance was defined as a p value of 0.05.
Univariable and multivariable linear regressions, on the other hand, were used to identify factors linked with regimen weariness.To begin, the statistical assumptions of linear regression analysis were put to the test.The Pearson R statistical test was used to calculate correlations between research variables.The multivariable linear regression analysis included all predictor variables with p values less than 0.25 in the univariable linear regression analysis.The overall model (F statistic, degrees of freedom, and p-value) was then reported, as was the variance explained by the overall model (adjusted r 2 ) and any significant independent variables in the model (unstandardized beta coefficient, p-value).
Thematic analysis was used to assess the qualitative data.To aid with data analysis, the NVivo 12 qualitative data analysis program (QSR International Pty Ltd.Version 12, 2018) was employed.The data was first evaluated by verbatim transcribing the recorded data from Amharic to English, and then the transcript was classified and grouped into themes.Two investigators (OSM and MH) independently transcribed the audio recordings verbatim and read all of the participants' interview notes.The four investigators were in charge of coding, categorizing, and developing themes.Each theme's concepts were presented, narrated, and triangulated with quantitative findings.

Operational definitions
Treatment Burden Global Score-the sum of all items scores of the questionnaire with 'does not apply' and missing answer considered the lowest possible score (0) [scores ranging from 0 to 150].No Treatment Burden-a score of 0 for each item in the TBQ.Low Treatment Burden-a TBQ global score of < 59. High Treatment Burden-a TBQ global score of ≥ 59.Treatment Regimen Fatigue-waning commitment to continue with a prescribed long-term treatment.Limited Health Literacy-if participants 'sometimes' or 'often' or 'always' need reading help for written health materials related to DM and HIV.Poor Medications Availability -if medications are available 'sometimes' , 'rarely' , 'not at all' as self-reported by the patient.Poor Knowledge of DM/HIV-if patients responded 'insufficient' or 'very insufficient' when asked about their knowledge about HIV/AIDS and Diabetes (e.g., symptoms, disease progression) and its treatment protocols (e.g., possible side effects, expected benefits, other treatment options).Poor family support-if patients does not obtain family/caregiver support (physical, psychological, financial) in self-management of their disease.Comorbidity-presence of two or more concurrent illnesses other than the primary diseases (HIV-AIDS and Diabetes Mellitus).

Ethical approval and informed consent
The study was approved by the Ethical Review Board (ERB) of Addis Ababa University, College of Health Sciences (25/03/2021; ERB No. 259/13/2021).The study protocol was performed in accordance with the Declaration of Helsinki.The aim and protocol of the current study were fully explained to all participants included in the study and written informed consent was obtained from all participants.All obtained data were treated confidentially.

Clinical characteristics of the study participants
The median (IQR) duration of DM/HIV was 10 (6-16) years, and about 83.5% had type 2 DM.Most participants 212(70.7%)had to travel an hour and more to reach to the respective clinics.About 205(68.3%) of the participants were presented with other comorbid diseases (Table 2).

Treatment related characteristics of the study participants
Participants took an average of 4.19 ± 3.19 pills daily.With regards to ADR, 69(23.0%) of them reported adverse drug effects.Nearly half of the study participants (52.3%) obtained their refill medications via health insurance system.Majority of the participants 138(46.0%)had two or more comorbid conditions.Out of which, half of them (50.0%) were presented with hypertension, then followed by cardiac diseases (39.0%), and dyslipidemia (13.7%) (Table 3).

Factors associated with treatment burden
The multivariable binary logistic regression model unveiled that presence of two and more comorbidities adjusted odd ratio [AOR] = 7.95, 95% CI 1.59-39.08),daily ingestion of more than five types of prescribed medications (AOR = 6.81, 95% CI 1.59-29.14),and good knowledge about DM/HIV and their treatment protocols (AOR = 0.33, 95% CI 0.12-0.92)were found to be predictors of higher burden of treatment (Table 5).

Factors associated with treatment regimen fatigue
Correlational analysis examining the association between potential antecedent factors and TRF indicated that number of comorbidities (r = 0.125; p = 0.030) was significantly correlated with TRF (see supplementary Table S1).

Qualitative analysis of patients' and health care workers' propositions to decrease treatment burden and regimen fatigue
Three major themes were extracted from patients and health care workers propositions on how burden of treatment and regimen fatigue could be ameliorated.(1) Fostering self-care efficacy, (2) Advancing the administrative services of the clinic and the hospital, and (3) Improving the healthcare system provision.Then, subthemes along with excerpts emerged in each key theme (see Supplementary Tables S4 and S5).
Theme 1: fostering self care efficacy Patients proposed to modify the complexity of treatment regimens and contents of counseling tips as a means of developing self-care efficacy.To this end, one of the participants underscored that: www.nature.com/scientificreports/ In the process of patient consultation for HIV patients, awareness campaigns should be incorporated with special emphasis on the topics of stigma and fear of disclosure (P-11).
Consonant to the patient's perspective, health care workers advocate improving consultation content, providing patient education, establishing formalized patient support group system, and availing fixed-dose combination (FDC) medications to improve self-care management.
Regarding role of patient education, an experienced infectious disease fellow specialist serving in the HIV clinic iterated that: I think counseling on prescribed medication adherence along with its potential merits outweighs mere prescribing (HCP-2).Theme 2: advancing the administrative services of the clinic and the hospital Major issues emphasized by participants to upgrade the administrative services of the clinic or hospital include improving waiting area of the clinics, enhancing medication availability, reducing patient flow, promoting infrequent changing of physicians, and availing functional laboratory tests.
Most patients repeatedly iterated the importance of availing fully functional laboratory tests and hiring qualified laboratory technicians.To this end, one of the participants asserted that:

Surprisingly, crucial laboratory tests like HgbA1c, thyroid function tests, and viral load are unavailable in this big referral hospital causing us to look forward to other high-priced private institutions capable of undergoing these tests (P-12).
In conformity to the above statement, another participant stated that: The queue for undergoing lab tests is prodigious but the number of working lab technicians are few (usually not more than two).Owing to this, the service provided is quite slow.To overcome this, competent lab technicians should be hired (P-2).
In conformity to the patients' proposition, health care workers proposed to extend follow-up schedule and improve laboratory services of the hospital.To this end, an experienced endocrine fellow specialist serving in the diabetic clinic underscored as follows: I heard frequent complaints from patients pertaining to the service provided in the hospital's laboratory.To surmount this, many competent and well qualified lab technicians should be employed.If possible, because the diabetic clinic is one of the heavily burdened clinics in TASH, it is good to establish a separate lab for the clinic where only DM related tests will be performed (HCP-1).www.nature.com/scientificreports/Theme 3: improving the health care system provision Patients conceived that the ripest way for boosting health care system provision is via obtaining social support, developing communication skills of non-medical staffs, and strengthening health insurance system.Regarding social support, one participant claimed that: I believe that social help from a government and/or sponsoring organization in the form of financial aid or job opportunity is a weapon for transforming the health care system (P-3).
As reiterated by the health care workers, establishing a link between health insurance office and Kenema pharmacy, advancing the electronic record (I-Care) system, launching a well-organized health insurance system, and providing financial support have paramount role to upgrade the provision of the health care system.
With respect to the I-care system, one of the nurses who had 10-year work experience in the diabetic clinic asserted that:

Discussion
This study is the pioneer to explore the treatment burden and regimen fatigue of patients with HIV/AIDS and DM from the perspective of both health care workers and patients in SSA health care context, particularly in Ethiopia, using a mixed method study approach.Unfortunately, quite a few quantitative based-studies are available to compare our results owing to the novelty of conceptualizing and measuring TB and TRF in the aforementioned disease contexts.The current study finding revealed a mean global TBQ of 28.86 (SD = 22.13).This finding is consonant with the findings of a study conducted in Switzerland (mean = 26.8,SD = 18.6) 21.Though the specific disease context is different (heart failure), the finding is consistent with a recent study done in Ethiopia using similar patientreported outcome measure [TBQ] (mean = 27.2,SD = 19.4) 20.Conversely, it is smaller as compared to the studies conducted in USA, Cleveland State, (mean = 37.0, SD = 24.5) 22, Australia (mean = 56.5,SD = 34.5) 23, Qatar (Median = 40.5,IQR = 38) 24 , Côte d'Ivoire (mean = 33.3,SD = 19.6) 2 , and larger than a study done in USA, Ohio State, (mean = 22.8, SD = 24.6) 25 .The incongruity might be ascribed to the differences in the quality of health care provided, fragmented, and disorganized health care system provision, and varied economic capability.Our study determined the level of TB/TRF solely from the perspective of HIV and diabetic population alone.
In this study, highest level of TB was reported in administrative (mean = 9.05, SD = 9.4), medication (mean = 5.98, SD = 8.2) and social (mean = 5.93, SD = 6.1) domains, while lowest value of TB was displayed by lifestyle change (mean = 4.06, SD = 5.0) and financial (mean = 3.84, SD = 4.2) domains.This finding is incongruent with studies done in Australia 23 that reported highest TB on financial, lifestyle, social, administrative, and medication domains, respectively and in Qatar 24 that showed highest TB on medication, lifestyle, administrative, social and financial domain, respectively and in Ethiopia 20 that showed administrative, financial, lifestyle, social, and medication domains, respectively.The possible reason behind such discrepancies could be attributed to the differences in the quality of the health care provided, disorganized healthcare system, economic factors, and specific disease context.
The present study findings revealed that about 265(88.3%) of participants reported low burden, and only 35(11.7%)indicated high burden.This finding is incongruent to Tran's et al. 26 study, where roughly 47% experienced low, 28% moderate, and 24% high onerousness.Contrary to our finding, Bekalu' et al. 27 recently found moderate (58.9%) to high (26.2%)level of medication related burden and Baah-Nyarkoh et al. 28 indicated 69.3% patients as having minimal burden in diabetic patients.The inconsistency could be attributed to variations in the characteristics of the study subjects.For instance, Tran's and Bekalu's incorporated a large sample comprised of slightly older, and highly educated subjects.The discrepancy could also be colligated to difference on the Table 4. Analysis of five domains of TBQ among adult HIV and DM patients attending TASH.

Variables
Mean ± SD 1. Medication related burden 5.98 ± 8.27 Problems with the flavor, shape, or size of your drug, as well as discomforts induced by your injection (such as pain, bleeding, bruising, or scarring)?1.61 ± 2.75 Problems caused by the number of times per day you must take your prescriptions (for example, once per day/twice per day)?1.54 ± 2.88 Problems caused by the efforts required to remember to take your prescriptions (for example, not quitting taking medication when you are away from home, organizing and utilizing a pillbox……)?1.48 ± 2.69 Problems caused by the precautions you must take when taking your prescriptions (for example, taking them at specified times or meals as suggested by your doctor, avoiding driving or lying down after taking meds, etc.)? 1.35 ± 2.41 2. Administrative related burden 9.05 ± 9.42 Problems with the time required to undergo lab tests and other associated procedures on a regular basis (for example, blood testing or radiology)?2.89 ± 3.78 Problems with the time required to self-monitor your health state on a regular basis (for example, monitoring your blood pressure or BGL)? 0.71 ± 0.88 Problems with the time required to attend doctor visits and other medical appointments on a regular basis, as well as difficulty in locating health care professionals? 1. 27   20,30 .Furthermore, this study unveiled that having sufficient knowledge about DM/HIV and its treatment protocol and availability of medications was strongly associated with lower TB.This finding in agreement with Hassen et al., study 20 though the specific disease context is different (DM/HIV vs Heart Failure).Even with differences in disease context, knowledge and medication availability have massive impact for both diseases owing to their chronic nature.Moreover, this finding is consistent with previous qualitative studies 31,32 .
Regarding TRF, the finding of this study demonstrated that poor availability of medications was significantly associated with TRF of HIV and diabetic patients.This finding is novel because so far, the available studies did not quantitatively examine its association with TRF.However, this finding was supported by previous qualitative studies by Claborne et al. 33 , and Crowford et al. 34 , which showed that TRF may be precipitated by the agglomerative effects of treatment, physical, psychosocial, cognitive, and economical-related factors.
As evidenced from the qualitative finding of this study, patients genuinely proposed for boosting self-care efficacy, administrative services of the clinic and/or the hospital, and health care system provision to alleviate and/or prevent the occurrence of TB and TRF.This finding is in line with a previous study by Ting et al., which indicated that patients suggestions to ameliorate treatment onerousness were focused on better provision of health care services and access, and rendering a less burdensome regimen 32 .Perhaps, this finding is supported by a study by Tran et al. which unveiled that patient proposed to improve personal care and the hospital's organization and the health care system 2 .Apparently, the present study found that health care workers perspectives on decreasing TB and TRF strongly aligns with patients' perspectives, especially concerning to the laboratory set-up and service.
Unfortunately, some of the propositions raised by patients in the current study were comparable as those underscored by patients residing in developed countries though clear difference was noted in terms of the magnitude of their impact on patients' lives.For example, financial constraints associated with transportation and refilling medications was unbearable in this study and thus most patients emphasized having social and/or financial support and availing of less costly medications.In contrary, in developed countries like France and Chile, health care services are delivered free of charge to ambulatory patients presenting with any chronic diseases.Indeed, the variety of patients and health care workers propositions spotlighted that there is no 'one-size-fits-all' approach to minify TB and TRF and healthcare must be tailored to fit each patient's context.
Finally, this study has some limitations that need to be acknowledged.First, it investigated TB and TRF at a single point in time cross-sectionally.Second, some variables such as smoking habit, disease duration, daily number of pills were obtained directly from patients which may cause social desirability and recall bias.Third, interviewer administration approach was applied to collect the quantitative data using TBQ and TRFS that may eventually lead to social desirability bias.To trim this risk, all data collectors strictly followed the interview protocols and avoided any personal knowledge, beliefs, and influences.Fourth, it was confined to HIV and diabetic patients who could speak Amharic language only and thus may not be generalized to other cultures or countries with other types of chronic medical illnesses.Fifth, the TBQ-15 and TRFS tools were culturally adapted and implemented, however, except internal consistency no further psychometric testing was done.

Conclusion
The findings of this study unveiled that a considerable proportion of patients faced low levels of TB and TRF.Our finding revealed that the presence of two or more comorbidities, daily intake of more than five types of prescribed medications, and disease knowledge were found to have statistically significant associations with high TB.This study also showed that poor medication availability was significantly associated with TRF.The qualitative findings of this study unveiled that fostering self-care efficacy, administrative services of the clinic/hospital, and the health care provision had paramount importance in reducing TB and TRF.Multiple factors that increase TB and TRF should be considered when designing specific healthcare interventions toward HV and diabetic patients to achieve the desired goals of therapy.

Table 2 .
Clinical characteristics of HIV and diabetic patients attending adult ART and DM clinic of TASH, Addis Ababa, Ethiopia, February 01-March 30, 2022 (n = 300).DM diabetes mellitus, HIV human immune deficiency virus, No number, Hx history, Appo appointment, IQR inter quartile range, SD standard deviation.

Table 5 .
Univariable and multivariable logistic regression analysis of factors associated with treatment burden among HIV and diabetic patients attending ART and DM clinic of TASH, Addis Ababa, Ethiopia, February 01-March 30, 2022 (n = 300).COR crude odds ratio, AOR adjusted odds ratio, CI confidence interval, Appo appointment, Dx disease, ADR adverse drug reaction, No number, mon month, Med medication.*Significant at p < 0.05., complex treatment regimens, erratic medication taking behavior, and uninterrupted motivation.This study revealed that more intake of prescribed medications (> 5 types) was strongly linked with higher TB.Similar observations were noted in studies by Morris et al., and Hassen et al., which showed that high TB was strongly associated with more prescribed regular medications polypharmacy